Mutagenetix > Incidental Mutation

Incidental Mutation 'R3843:Pdp1'

277237

Institutional Source

Beutler Lab

Gene Symbol

Pdp1

Ensembl Gene

ENSMUSG00000049225

Gene Name

pyruvate dehydrogenase phosphatase catalytic subunit 1

Synonyms

LOC381511, Ppm2c

MMRRC Submission

040783-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R3843 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

11958183-11966450 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 11961961 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Glutamic Acid at position 117 (K117E)

Ref Sequence

ENSEMBL: ENSMUSP00000103937 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000056050] [ENSMUST00000095144] [ENSMUST00000108297] [ENSMUST00000108299] [ENSMUST00000108301] [ENSMUST00000108302]

AlphaFold

Q3UV70

Predicted Effect

probably benign
Transcript: ENSMUST00000056050
AA Change: K77E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000050521
Gene: ENSMUSG00000049225
AA Change: K77E

Domain	Start	End	E-Value	Type
PP2Cc	99	523	3.36e-97	SMART
PP2C_SIG	177	525	2.77e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000095144
AA Change: K102E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000092766
Gene: ENSMUSG00000049225
AA Change: K102E

Domain	Start	End	E-Value	Type
PP2Cc	124	548	3.36e-97	SMART
PP2C_SIG	202	550	2.77e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000108297
AA Change: K77E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000103932
Gene: ENSMUSG00000049225
AA Change: K77E

Domain	Start	End	E-Value	Type
PP2Cc	99	523	3.36e-97	SMART
PP2C_SIG	177	525	2.77e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000108299
AA Change: K102E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000103934
Gene: ENSMUSG00000049225
AA Change: K102E

Domain	Start	End	E-Value	Type
PP2Cc	124	548	3.36e-97	SMART
PP2C_SIG	202	550	2.77e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000108301
AA Change: K136E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000103936
Gene: ENSMUSG00000049225
AA Change: K136E

Domain	Start	End	E-Value	Type
low complexity region	11	18	N/A	INTRINSIC
PP2Cc	158	582	3.36e-97	SMART
PP2C_SIG	236	584	2.77e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000108302
AA Change: K117E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000103937
Gene: ENSMUSG00000049225
AA Change: K117E

Domain	Start	End	E-Value	Type
PP2Cc	139	563	3.36e-97	SMART
PP2C_SIG	217	565	2.77e0	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146154

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000154194

Meta Mutation Damage Score

0.0683

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.6%
20x: 96.0%

Validation Efficiency

100% (35/35)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Pyruvate dehydrogenase (E1) is one of the three components (E1, E2, and E3) of the large pyruvate dehydrogenase complex. Pyruvate dehydrogenase kinases catalyze phosphorylation of serine residues of E1 to inactivate the E1 component and inhibit the complex. Pyruvate dehydrogenase phosphatases catalyze the dephosphorylation and activation of the E1 component to reverse the effects of pyruvate dehydrogenase kinases. Pyruvate dehydrogenase phosphatase is a heterodimer consisting of catalytic and regulatory subunits. Two catalytic subunits have been reported; one is predominantly expressed in skeletal muscle and another one is is much more abundant in the liver. The catalytic subunit, encoded by this gene, is the former, and belongs to the protein phosphatase 2C (PP2C) superfamily. Along with the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinases, this enzyme is located in the mitochondrial matrix. Mutation in this gene causes pyruvate dehydrogenase phosphatase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]

Allele List at MGI

Other mutations in this stock

Total: 35 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aass	A	T	6: 23,092,495 (GRCm39)	Y168*	probably null	Het
Amt	C	T	9: 108,174,420 (GRCm39)	R62C	possibly damaging	Het
Arid2	C	T	15: 96,249,721 (GRCm39)	T145I	possibly damaging	Het
Ccdc8	T	C	7: 16,729,039 (GRCm39)	V176A	probably damaging	Het
Cdhr1	G	T	14: 36,806,884 (GRCm39)	F440L	probably benign	Het
Ckap2	A	T	8: 22,665,774 (GRCm39)	N424K	probably damaging	Het
Col6a1	C	T	10: 76,547,175 (GRCm39)	R730H	unknown	Het
Dennd1b	C	A	1: 138,981,092 (GRCm39)	P102Q	probably damaging	Het
E2f1	A	G	2: 154,402,748 (GRCm39)	S340P	probably benign	Het
Eef1akmt2	C	T	7: 132,433,305 (GRCm39)	V134I	probably damaging	Het
Elp3	A	T	14: 65,802,932 (GRCm39)		probably null	Het
Grap	T	G	11: 61,551,151 (GRCm39)		probably null	Het
Heatr1	T	C	13: 12,450,002 (GRCm39)	Y1999H	probably benign	Het
Hectd4	G	T	5: 121,397,936 (GRCm39)	W288L	possibly damaging	Het
Hnf4g	G	A	3: 3,716,362 (GRCm39)	C262Y	probably benign	Het
Hrh4	A	G	18: 13,155,343 (GRCm39)	Y294C	possibly damaging	Het
Igkv5-39	C	A	6: 69,877,526 (GRCm39)	G77W	probably damaging	Het
Kdm2b	A	T	5: 123,072,856 (GRCm39)	Y341N	probably damaging	Het
Kif26b	T	C	1: 178,755,742 (GRCm39)	L1952P	probably damaging	Het
Lgr4	C	T	2: 109,827,118 (GRCm39)		probably benign	Het
Nlrc3	G	A	16: 3,782,828 (GRCm39)	R194W	probably benign	Het
Nup214	T	C	2: 31,941,112 (GRCm39)	F547L	probably damaging	Het
Or5m3	A	G	2: 85,838,548 (GRCm39)	I143V	probably benign	Het
Phtf2	G	A	5: 20,979,020 (GRCm39)	A31V	probably damaging	Het
Pip4p2	T	A	4: 14,886,553 (GRCm39)	Y42*	probably null	Het
Pkhd1	A	T	1: 20,628,947 (GRCm39)	C667S	probably benign	Het
Pnp2	T	A	14: 51,200,878 (GRCm39)	L121Q	probably null	Het
Ppfia1	C	T	7: 144,058,707 (GRCm39)	R698Q	probably benign	Het
Sidt1	A	T	16: 44,104,587 (GRCm39)	F275I	probably benign	Het
Slc50a1	A	T	3: 89,177,207 (GRCm39)	I70N	probably damaging	Het
Sytl2	C	G	7: 90,009,367 (GRCm39)	T123R	possibly damaging	Het
Tlk1	T	A	2: 70,579,671 (GRCm39)	T214S	probably benign	Het
Tmco3	A	G	8: 13,346,114 (GRCm39)		probably benign	Het
Trim71	T	C	9: 114,344,914 (GRCm39)	T335A	probably benign	Het
Zbtb47	T	A	9: 121,592,499 (GRCm39)	V273E	possibly damaging	Het

Other mutations in Pdp1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02243:Pdp1	APN	4	11,961,873 (GRCm39)	missense	probably benign	0.20
IGL02643:Pdp1	APN	4	11,962,062 (GRCm39)	missense	probably benign
R1931:Pdp1	UTSW	4	11,962,074 (GRCm39)	missense	probably benign	0.01
R2162:Pdp1	UTSW	4	11,961,123 (GRCm39)	missense	probably damaging	0.98
R2418:Pdp1	UTSW	4	11,961,838 (GRCm39)	missense	probably damaging	0.98
R5699:Pdp1	UTSW	4	11,960,907 (GRCm39)	missense	possibly damaging	0.79
R6479:Pdp1	UTSW	4	11,961,327 (GRCm39)	missense	probably damaging	1.00
R7221:Pdp1	UTSW	4	11,961,004 (GRCm39)	missense	probably damaging	0.99
R7263:Pdp1	UTSW	4	11,960,821 (GRCm39)	missense	possibly damaging	0.82
R8483:Pdp1	UTSW	4	11,961,982 (GRCm39)	missense	probably benign
R9184:Pdp1	UTSW	4	11,962,143 (GRCm39)	missense	possibly damaging	0.80
R9712:Pdp1	UTSW	4	11,961,607 (GRCm39)	missense	probably benign	0.41
Z1177:Pdp1	UTSW	4	11,961,639 (GRCm39)	missense	possibly damaging	0.67

Predicted Primers

PCR Primer
(F):5'- CTTTCACTGACTGCCTGGGAAC -3'
(R):5'- TGGCACTGCATGTTACTGCC -3'

Sequencing Primer
(F):5'- AGCATCCCTCTGGTCTGCAAG -3'
(R):5'- ACTGCATGTTACTGCCACCAC -3'

Posted On

2015-04-06